title: Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization.
abstract: Allergen-specific immunoglobulin E (present in allergic sensitization) has a central role in the pathogenesis of allergic disease. We performed the first large-scale genome-wide association study (GWAS) of allergic sensitization in 5,789 affected individuals and 10,056 controls and followed up the top SNP at each of 26 loci in 6,114 affected individuals and 9,920 controls. We increased the number of susceptibility loci with genome-wide significant association with allergic sensitization from three to ten, including SNPs in or near TLR6, C11orf30, STAT6, SLC25A46, HLA-DQB1, IL1RL1, LPP, MYC, IL2 and HLA-B. All the top SNPs were associated with allergic symptoms in an independent study. Risk-associated variants at these ten loci were estimated to account for at least 25% of allergic sensitization and allergic rhinitis. Understanding the molecular mechanisms underlying these associations may provide new insights into the etiology of allergic disease.
authors.affiliation: COPSAC, Copenhagen Prospective Studies on Asthma in Childhood; Health Sciences, University of Copenhagen & Copenhagen University Hospital, Gentofte, Denmark.
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authors.lastname: Bønnelykke
authors.affiliation: Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne, Melbourne, Australia.
authors.forename: Melanie C
authors.initials: MC
authors.lastname: Matheson
authors.affiliation: Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark.|Division of Endocrinology, Children's Hospital, Boston, USA.|Center for Basic and Translational Obesity Research, Children's Hospital, Boston, USA.|Broad Institute, Cambridge, USA.
authors.forename: Tune H
authors.initials: TH
authors.lastname: Pers
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Raquel
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authors.lastname: Granell
authors.affiliation: Division of Population Health Sciences & Education, St George's, University of London, London, UK.
authors.forename: David P
authors.initials: DP
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authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK.
authors.forename: Alexessander Couto
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authors.affiliation: Research Centre for Prevention and Health, Glostrup Hospital, Glostrup, Denmark.
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authors.lastname: Linneberg
authors.affiliation: University of Manchester, Manchester Academic Health Science Centre, University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
authors.forename: John A
authors.initials: JA
authors.lastname: Curtin
authors.affiliation: School of Women's and Infants' Health, The University of Western Australia, Crawley, Australia.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Warrington
authors.affiliation: Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Marie
authors.initials: M
authors.lastname: Standl
authors.affiliation: Department of Epidemiology, Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
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authors.forename: Ingileif
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authors.forename: Blazenka K
authors.initials: BK
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authors.affiliation: Institute of Health Sciences, University of Oulu, Oulu, Finland.|Biocenter Oulu, University of Oulu, Oulu, Finland.
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authors.affiliation: deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland.
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authors.affiliation: deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland.|University of Iceland, 101 Reykjavik, Iceland.
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authors.affiliation: Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
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authors.affiliation: Lung Institute of WA, University of WA, Perth, Western Australia, Australia.|Centre for Asthma, Allergy and Respiratory Research, University of WA, Perth, Western Australia, Australia.
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authors.affiliation: COPSAC, Copenhagen Prospective Studies on Asthma in Childhood; Health Sciences, University of Copenhagen & Copenhagen University Hospital, Gentofte, Denmark.
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authors.affiliation: University of Manchester, Manchester Academic Health Science Centre, University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
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authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
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authors.affiliation: PathWest Laboratory Medicine of Western Australia (WA), Nedlands, Australia.|School of Population Health, The University of WA, Nedlands, Australia.|School of Pathology and Laboratory Medicine, The University of WA, Nedlands, Australia.|Busselton Population Medical Research Foundation, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
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authors.affiliation: Institute of Epidemiology I, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
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authors.initials: CMT
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authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
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authors.initials: SM
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authors.affiliation: Lung Institute of WA, University of WA, Perth, Western Australia, Australia.|Centre for Asthma, Allergy and Respiratory Research, University of WA, Perth, Western Australia, Australia.
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authors.affiliation: Queensland Institute of Medical Research, Brisbane, Australia.
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authors.affiliation: Queensland Institute of Medical Research, Brisbane, Australia.
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authors.initials: GW
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authors.forename: Anna-Liisa
authors.initials: AL
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authors.affiliation: Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne, Melbourne, Australia.
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authors.initials: SC
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authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
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authors.lastname: Herder
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authors.affiliation: Busselton Population Medical Research Foundation, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.|School of Medicine and Pharmacology, University of WA, Nedlands, Australia.|Department of Pulmonary Physiology, West Australian Sleep Disorders Research Institute, Nedlands, Australia.
authors.forename: Alan
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authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
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authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
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authors.initials: JN
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authors.affiliation: University of Manchester, Manchester Academic Health Science Centre, University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
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authors.affiliation: School of Women's and Infants' Health, The University of Western Australia, Crawley, Australia.
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authors.initials: CE
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authors.affiliation: Institute of Health Sciences, University of Oulu, Oulu, Finland.|Biocenter Oulu, University of Oulu, Oulu, Finland.|Department of Epidemiology and Biostatistics, School of Public Health, MRC-HPA Centre for Environment and Health, Imperial College London, UK.|National Institute of Health and Welfare, Oulu, Finland.|Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
authors.forename: Marjo-Riitta
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authors.lastname: Koppelman
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authors.affiliation: Queensland Institute of Medical Research, Brisbane, Australia.
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authors.affiliation: COPSAC, Copenhagen Prospective Studies on Asthma in Childhood; Health Sciences, University of Copenhagen & Copenhagen University Hospital, Gentofte, Denmark.
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authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
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mesh_terms: D000483:Alleles; D019295:Computational Biology; D053263:Gene Regulatory Networks; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D023281:Genomics; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D015398:Signal Transduction